Yangjing Capsule Alleviates Spermatogenic Dysfunction in Mice by Inhibiting the QKI-5/p38 MAPK Pathway Through Upregulation of IncRNA NONMMUT031883.2

Spermatogenic dysfunction is an important cause of male infertility, and cyclophosphamide (CP) can impair spermatogenesis by inducing abnormal spermatogonial apoptosis. Yangjing Capsule (YC) has been used to improve reproductive function, but its underlying molecular mechanism remains unclear. This study investigated the protective effects of YC in a CP-induced mouse model of spermatogenic dysfunction and in GC-1 spermatogonial cells. Sperm count and motility, male fertility, serum sex hormone levels, and histopathological changes in the testes and epididymides were evaluated. Cell viability, lactate dehydrogenase release, apoptosis, and apoptosis-related proteins were assessed in GC-1 cells. Quantitative reverse transcription polymerase chain reaction, RNA pull-down assays, immunofluorescence, and Western blotting were used to examine lncRNA NONMMUT031883.2, Quaking-5 (QKI-5), and p38 mitogen-activated protein kinase (MAPK) signaling. YC dose-dependently improved sperm quality, serum sex hormone levels, reproductive organ morphology, testicular histopathology, and fertility in CP-treated mice. In GC-1 cells, YC increased cell viability and reduced cellular damage and apoptosis. LncRNA NONMMUT031883.2 physically interacted with QKI-5, and YC treatment increased lncRNA NONMMUT031883.2 expression while reducing QKI-5 expression and p38 phosphorylation. YC treatment inhibited apoptosis induced by lncRNA NONMMUT031883.2 knockdown in GC-1 cells, whereas QKI-5 overexpression reduced the anti-apoptotic effects of YC. These findings suggest that YC alleviates CP-induced spermatogenic dysfunction and that its protective effects are mediated by regulation of the lncRNA NONMMUT031883.2/QKI-5/p38 MAPK pathway.